Immune globulin (IG) products from human plasma were first used in 1952 to treat immune deficiency. Initially, intramuscular or subcutaneous administrations of IG were the methods of choice. For injecting larger amounts of IG necessary for effective treatment of various diseases, however, intravenous administrable products with lower concentrated IG (50 mg/mL) were developed. The intravenous (IV) administration of immune globulin (IVIG) is the primary treatment of individuals with immune deficiencies. Although the initial IVIG preparations caused severe side effects, the IVIG preparations available at the present time are well tolerated in the majority of immune deficient patients. Nonetheless, a small proportion of patients continue to have unpleasant, even disabling, reactions such as headache, fatigue, and myalgia. Fever and chills remains a problem, especially when patients have intercurrent infections. The reactions often persist despite trying other IVIG preparations or pre-medicating with acetaminophen, diphenhydramine, and corticosteroids. Further, due to the requirement for IV administration, there are issues with patient compliance.
Subcutaneous (SQ) administration of immune globulin is an alternative to intravenous administration. Compared to IV infusions, SQ administration of immune globulin has several advantages. For example, it reduces the incidence of systemic reactions, does not require sometimes-difficult IV access, improves trough levels, and gives patients more independence.
For therapeutic use of any IG preparation, another important consideration in IG products is their stability during storage. Safe handling and administration of formulations containing proteins represent significant challenges to pharmaceutical formulators. Proteins possess unique chemical and physical properties that present stability problems: a variety of degradation pathways exist for proteins, implicating both chemical and physical instability. Chemical instability includes deamination, aggregation, clipping of the peptide backbone, and oxidation of methionine residues. Physical instability encompasses many phenomena, including, for example, aggregation. Hence, there is a need for stable formulations of immune globulin preparations.